Diane Robins, Ph.D.

Administrative Contact

Sue Kellog

Areas of Interest

We study gene regulation by steroid hormones, focusing on transcriptional mechanisms, hormone-dependent cancers, and sex-dependent gene modulation. Steroid receptors are ligand-activated transcription factors with diverse functions, yet several act via common DNA binding sites and interact with common coregulators. We examine how specific gene control is attained by the androgen receptor (AR).

To study the central role of AR in prostate cancer and to model human disease, we converted the mouse gene to the human sequence (humanized AR mice). Variant hAR alleles in mice confer differences in cancer initiation, progression, and response to therapy. This allows us to study mechanisms of treatment resistance, particularly by somatic AR mutation. In both mouse and human tumors, AR mutants use diverse mechanisms to evade therapy. We are using Next Generation Sequencing to profile differential gene expression and alternative regulatory networks, to improve prognosis and anti-AR treatments.

Sex differences in gene expression occur widely, impacting physiology and incidence of many diseases. We identified via mutant mice a KRAB zinc finger repressor (Regulator-of-sex-limitation) that influences sex-biased expression in liver of genes acting in lipid and steroid metabolism. Rsl deficiency leads to early puberty, lack of dietary stress response and susceptibility to obesity and diabetes. Rsl provides insight into KRAB-ZFP epigenetic mechanisms as well as evolution of this recently expanded gene family.